The use of implantable medical devices such as grafts, stents, and the like, has increased steadily since these devices were first developed. Stents or grafts are usually implanted into a variety of body vessels or lumens in an effort to maintain their patency and are particularly useful, for example, in the treatment of vascular diseases such as atherosclerotic stenosis or aneurysms in blood vessels.
In order for implantable medical devices to successfully perform their function, they must be biocompatible. In particular, it is important for a graft to be porous so as to allow cell ingrowth so that the graft becomes an integrated part of the body lumen. The graft must also be biologically inert so as to avoid excessive tissue growth, scarring, and blocking of the graft. A particularly advantageous compound for forming the graft is PTFE. This polymer is biocompatible as it is biologically inert and can be formed into appropriately sized lumens or tubes to meet various arterial and vascular needs. Furthermore, the method of making PTFE tubes, especially expanded PTFE (ePTFE) tubes, produces a desirable porosity. This feature encourages incorporation of the graft material into the body lumen while avoiding excessive cell growth, scarring, and blockage. However, use of PTFE in making grafts results in a product that is not radiopaque.
For a number of reasons, it is important to be able to see the implanted medical device using fluoroscopic methods. Fluoroscopy is useful in facilitating the precise placement during implantation of medical devices such as grafts or stents. After initial placement, fluoroscopy is useful in monitoring the status of the structure. Characteristics of a flexible graft that may be monitored using fluoroscopy include location of the graft, compliance of the graft, the anastomosis of the graft to the patient's body organ tubing, and the presence or absence of conditions such as holes, kink failures, bursts, aneurysm, and the like.
To date, a number of methods and devices have been developed that impart radiopacity to medical devices and/or implantation devices in order to satisfy these needs. For implantation of medical devices, a variety of radiopaque guide wires have been developed. The guide wire is usually inserted into the medical device and this assembly is guided through and inserted into a lumen of the body. The wire is usually made of an inherently radiopaque material. Placement of the medical device is tracked by fluoroscopically observing the wire as it guides the medical device into place. The disadvantage of this method is that once the medical device is in place, the radiopaque wire is removed. As a result, the implanted medical device remains invisible to fluoroscopic analysis after implantation.
One method of rendering medical devices detectable by fluoroscopy is the use of radiopaque metal markers placed directly on the medical device either at the ends or along the length of the device. See, for example, U.S. Pat. No. 6,253,769. These markers are of limited use in fluoroscopic detection of the flexible graft characteristics detailed above. Since only a portion of the graft is visible, holes and the like will go undetected. Furthermore, these markers are not particularly useful in implantable devices that are required to be porous and flexible, such as vascular prosthesis. Vascular grafts, including those which are surgically implanted and those which are introduced intraluminally, are designed to mimic the natural vessels and hence require a unique combination of features to be present. The graft must be sufficiently porous to allow formation of the altima, and encapsulation by the body, yet be fluid-tight to prevent leakage of blood. Additionally, flexibility and compliance are also key features of a successful graft product. Thus, use of metal bands or conventional radiopaque markers are unacceptable in such devices.
Fluoroscopically visible medical devices are known which use radiopaque polymers. Larsen, European Patent Publication No. 0 203 833, discloses a composition comprising a x-ray contrasting thermoset polymer including a crosslinkable polyester resin dissolved in a vinyl monomer. This composition may be used to manufacture surgical articles. However, due to the solid polymer's inflexibility, it may not be used to create flexible devices and would certainly be inappropriate to use as any type of prosthetic implant which requires flexibility.
U.S. Pat. No. 5,319,059 to Neuenschwander et al. discloses a biocompatible radiopaque material covalently attached to a polyurethane matrix. However, many polyurethane materials are known to be inherently unstable in the body over time, and may be reabsorbed into the body, rendering the article invisible by radiographic imaging. This may be problematic for applications to implantable articles, whose presence would become undetectable to X-rays after decomposition of the radiopaque material.
WO 90/03036 published application discloses use of polymer compositions having added inorganic heavy metal salts in a physical mixture for use in medical and dental applications. The heavy metal is present as a fine powder locked in a matrix. However, preparation of these compositions may result in an uneven distribution of salt which has an adverse effect on the plasticity of the composition. Furthermore, the salts tend to gradually leach out of such matrices releasing toxic heavy metals into the system. Composite polymers are also known but these are only possible with polymers having appropriate reaction sites, such as carbonyl moieties. Thus, these composite polymers are not useful with PTFE grafts.
Fluoroscopically visible medical device are known which include detectable coatings. U.S. Pat. No. 4,990,138 discloses an everting balloon catheter that is made radiopaque by bonding a polymeric material doped with a major amount of radiopaque metals onto a distal end portion a catheter body. The coating allows the distal end to be visible for use in guiding placement of the catheter body.
U.S. Pat. No. 6,048,362 discloses a radiopaque filler compound added to an elastic polymer. The polymer is then coated onto a metal frame to form a stent/graft device. In preferred embodiments, the radiopaque material contains barium, bismuth, or tungsten, and the polymer is treated with a porous coating to improve bio-compatibility. The result is a fluoroscopically visible stent/graft device.
Published Application No. WO 01/49340 to Pacetti and Mroz discloses a stent having enhanced radiopacity due to particles of radiopaque material contained within a binder that is used as a coating for the stent. This invention is limited to use on stents.
It is also known to coat the interior of an implantable device with radiopaque metals such as gold, platinum and tantalum by sputtering, evaporation or electroplating processes. It is a requirement of these coatings that they have good adhesion and conform to the medical device during deformation. Unfortunately, these coatings are susceptible to degradation over time. Cracking, flaking, and delamination can be a problem with this approach. When part of the coating separates from the substrate, there is a risk of causing turbulence in the blood flow and resultant thrombogenesis. Pieces may also create a risk of embolism in downstream vasculature.
While the prior art discloses various compositions and methods for rendering an implantable medical device radiopaque, there has yet to be developed an implantable medical device that is biocompatible, radiopaque, and does not lose effectiveness with time or risk injury to a patient. Thus, there is a present need for a radiopaque implantable medical device that is safe, biocompatible and biostable over time.